BTK

Btk inhibitor 1 R enantiomer hydrochloride can be utilized to create activity-based probes (ABPs) based on itrutinib and itrutinib itself [3].

[1]. A QUALITY BY DESIGN APPROACH FOR DEVELOPMENT OF SIMPLE AND ROBUST REVERSED PHASE STABILITY INDICATING HPLC METHOD FOR ESTIMATION OF IBRUTINIB AND ITS IMPURITIES.

[2]. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13075-80.

[3]. Direct and two-step bioorthogonal probes for Bruton's tyrosine kinase based on ibrutinib: a comparative study. Org Biomol Chem. 2015 May 14;13(18):5147-57.

Activation of the B-cell antigen receptor (BCR) signaling pathway promotes the development and maintenance of B-cell malignancies and autoimmune diseases. Bruton's tyrosine kinase (Btk) is essential for BCR signaling, and dysfunctional mutations in Btk in humans and mice block B-cell maturation, a critical step in the maturation process requiring a functional BCR pathway. This article introduces a selective and irreversible Btk inhibitor, PCI-32765, which is currently undergoing clinical development in patients with B-cell non-Hodgkin lymphoma. We used this inhibitor to investigate the biological effects of Btk inhibition on mature B-cell function and the progression of B-cell-related diseases. PCI-32765 blocks BCR signaling in human peripheral blood B cells at concentrations that do not affect T-cell receptor signaling. In a mouse model of collagen-induced arthritis, oral administration of PCI-32765 reduced circulating autoantibody levels and completely inhibited disease progression. PCI-32765 also inhibited autoantibody production and the development of kidney disease in an MRL-Fas(lpr) lupus model. Occupation of the Btk active site by PCI-32765 was monitored in vitro and in vivo using a Btk fluorescent affinity probe. Occupation of the Btk active site was closely associated with blockade of the BCR signaling pathway and in vivo efficacy. In addition, PCI-32765 induced an objective clinical response in dogs with spontaneous B-cell non-Hodgkin lymphoma. These findings support Btk inhibition as a treatment for human diseases associated with BCR pathway activation. [2]

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Ibrutinib is a covalent and irreversible Bruton's tyrosine kinase (BTK) inhibitor that has been approved for the treatment of hematologic malignancies such as chronic lymphocytic leukemia, mantle cell lymphoma and Waldenström macroglobulinemia. The covalent and irreversible nature of its molecular mode of action allows it to be identified and monitored in activity-based proteomic analysis (ABPP). In recent years, fluorescently labeled and biotinylated ibrutinib derivatives have been published for in vitro and in vivo monitoring of BTK. The work described herein complements existing methods and involves a comparative study of the effectiveness of direct and two-step bioorthogonal ABPP of BTK. [3]

C22H23CLN6O

422.9106

422.162

1553977-42-6

(Rac)-IBT6A;1412418-47-3;IBT6A;1022150-12-4;(Rac)-IBT6A hydrochloride;1807619-60-8

78357770

White to off-white solid

5.504

3

6

4

30

521

1

Cl[H].O(C1C([H])=C([H])C([H])=C([H])C=1[H])C1C([H])=C([H])C(=C([H])C=1[H])C1C2=C(N([H])[H])N=C([H])N=C2N([C@@]2([H])C([H])([H])N([H])C([H])([H])C([H])([H])C2([H])[H])N=1

ATLAMSZMAHXMSQ-PKLMIRHRSA-N

InChI=1S/C22H22N6O.ClH/c23-21-19-20(15-8-10-18(11-9-15)29-17-6-2-1-3-7-17)27-28(22(19)26-14-25-21)16-5-4-12-24-13-16;/h1-3,6-11,14,16,24H,4-5,12-13H2,(H2,23,25,26);1H/t16-;/m1./s1

3-(4-phenoxyphenyl)-1-[(3R)-piperidin-3-yl]pyrazolo[3,4-d]pyrimidin-4-amine;hydrochloride

1553977-42-6; Btk inhibitor 1 (R enantiomer hydrochloride); IBT6A (hydrochloride); IBT6A hydrochloride; Btk inhibitor 1 R enantiomer hydrochloride; Btk Inhibitor 1 R-Enantiomer Hydrochloride; (R)-3-(4-Phenoxyphenyl)-1-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine hydrochloride; 3-(4-phenoxyphenyl)-1-[(3R)-piperidin-3-yl]pyrazolo[3,4-d]pyrimidin-4-amine;hydrochloride;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~100 mg/mL (~236.5 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)